The Antihypertensives and Vascular, Endothelial and Cognitive Function Trial

NCT00605072 | Completed Phase 2 Results

• 2 other identifiers: IA0127K23AG030057
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to examine the effects of blood pressure medications on cognition and blood flow in hypertensive elderly patients with cognitive impairment. The hypothesis is that treatment with an angiotensin receptor blocker (ARB) or an angiotensin-converting enzyme inhibitor (ACEI) will be associated with a slower rate of further cognitive decline, improved cerebral blood flow and its regulation, and preserved physical function as compared to treatment with a diuretic (HCTZ), independent of blood pressure level.

Conditions

Cognitive Impairment; Hypertension; Aging

Keywords

cognitive disorders; angiotensin receptor blockers

Outcome Measures

Primary Outcomes (3)

• Cognitive Assessment: Trail Making Test Part B

  This test requires the connection of sequentially numbered circles (A), and the connection of circles marked by numbers and letters in alternating sequence (B). This test is considered a benchmark of executive function. The test score is the time required to complete the task in seconds.

  Baseline-12 months

• Cognitive Assessment: Hopkins Verbal Learning- Immediate Recall

  This is a 12-item list learning test in which individuals are presented three learning and recall trials followed by a delayed recall and 24 item recognition test. The HVLT-R has been identified as an ideal memory measure for elderly patients, and appropriate reliability and validity have been shown in older individuals. The test score is the number of correct answers in the delayed recall ( score range 0-12)

  Baseline-12 months

• Cognitive Assessment: Forward Digit Span Test

  This test consists of series of digits of increasing length, some of which are recited as presented, and some of which are to be recited in reversed order. The forward digit span score ranges from 0 (ie cannot repeat two digits) to 8 ( participant can repeat up to 8 digits)

  Baseline-12 months

Secondary Outcomes (2)

• Blood Pressure Outcome: Systolic BP

  Baseline-12 months

• Blood Flow Velocity, Sitting

  Baseline-12 months

Study Arms (3)

Candesartan

EXPERIMENTAL

Angiotensin Receptor Blocker

Drug: candesartan; Drug: nifedipine, long acting; Drug: metoprolol, long-acting

Lisinopril

EXPERIMENTAL

Angiotensin-Converting Enzyme (ACE) Inhibitor

Drug: lisinopril; Drug: nifedipine, long acting; Drug: metoprolol, long-acting

HCTZ

ACTIVE COMPARATOR

Hydrochlorothiazide (diuretic)

Drug: hydrochlorothiazide

Interventions

candesartan DRUG

orally 8 mg increased to 16 mg then 32 mg to achieve target blood pressure of 140/90, then daily for 12 months

Also known as: Atacand

Candesartan

lisinopril DRUG

orally 10 mg increased to 20 mg then 40 mg to achieve target blood pressure of 140/90, then daily for 12 months

Also known as: Prinivil

Lisinopril

hydrochlorothiazide DRUG

orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 12 months

Also known as: HCTZ, multiple brand names

HCTZ

nifedipine, long acting DRUG

If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

Also known as: Procardia XL

Candesartan; Lisinopril

metoprolol, long-acting DRUG

If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

Also known as: Lopressor, Toprol XL

Candesartan; Lisinopril

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• Hypertension
• Cognitive criteria: score either 10 or less out of 15 for the executive clock draw test 1 (CLOX1) or less than or equal to 1 standard deviation from the corresponding age specific mean on the immediate memory subtest

You may not qualify if:

• Intolerance to ACEI or ARB
• History of congestive heart failure
• History of diabetes mellitus
• History of stroke (less than 6 months)

Sponsors & Collaborators

• University of Southern California: lead
• National Institute on Aging (NIA): collaborator
• Hebrew SeniorLife: collaborator

Study Sites (2)

University of Southern California

Los Angeles, California, 90033, United States

Location

Hebrew SeniorLife

Boston, Massachusetts, 02131, United States

Location

Related Publications (4)

• Lipsitz LA, Gagnon M, Vyas M, Iloputaife I, Kiely DK, Sorond F, Serrador J, Cheng DM, Babikian V, Cupples LA. Antihypertensive therapy increases cerebral blood flow and carotid distensibility in hypertensive elderly subjects. Hypertension. 2005 Feb;45(2):216-21. doi: 10.1161/01.HYP.0000153094.09615.11. Epub 2005 Jan 17.

  PMID: 15655124 BACKGROUND

• Hajjar I, Hart M, Milberg W, Novak V, Lipsitz L. The rationale and design of the antihypertensives and vascular, endothelial, and cognitive function (AVEC) trial in elderly hypertensives with early cognitive impairment: role of the renin angiotensin system inhibition. BMC Geriatr. 2009 Nov 18;9:48. doi: 10.1186/1471-2318-9-48.

  PMID: 19922631 BACKGROUND

• Hajjar I, Hart M, Chen YL, Mack W, Milberg W, Chui H, Lipsitz L. Effect of antihypertensive therapy on cognitive function in early executive cognitive impairment: a double-blind randomized clinical trial. Arch Intern Med. 2012 Mar 12;172(5):442-4. doi: 10.1001/archinternmed.2011.1391. No abstract available.

  PMID: 22412114 RESULT

• Hajjar I, Hart M, Chen YL, Mack W, Novak V, C Chui H, Lipsitz L. Antihypertensive therapy and cerebral hemodynamics in executive mild cognitive impairment: results of a pilot randomized clinical trial. J Am Geriatr Soc. 2013 Feb;61(2):194-201. doi: 10.1111/jgs.12100. Epub 2013 Jan 25.

  PMID: 23350899 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction; Hypertension

Interventions

candesartan; candesartan cilexetil; Lisinopril; Hydrochlorothiazide; Nifedipine; Metoprolol

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Propanols; Amines

Limitations and Caveats

The main limitation is the small sample size. The validity of TCD measurements as an index of cerebral blood flow is based on the assumption that cerebral vessel diameters are constant but we didn't have brain imaging to validate this assumption.

Results Point of Contact

• Title: Dr. Ihab Hajjar
• Organization: University of Southern California

ihajjar@usc.edu

323-226-6720

Study Officials

• Ihab Hajjar, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: January 11, 2008
• First Posted: January 30, 2008
• Study Start: January 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2012
• Last Updated: February 15, 2013
• Results First Posted: February 15, 2013

Record last verified: 2013-01

Locations

US (2)